A Re-evaluation of the “Oncogenic” Nature of Wnt/β-catenin Signaling in Melanoma and Other Cancers

In cancer, Wnt/β-catenin signaling is ubiquitously referred to as an “oncogenic” pathway that promotes tumor progression. This review examines how the regulation and downstream effects of Wnt/β-catenin signaling in cancer varies depending on cellular context, with a focus on malignant melanoma. We emphasize that the cellular homeostasis of Wnt/β-catenin signaling may represent a more appropriate concept than the simplified view of the Wnt/β-catenin pathway as either oncogenic or tumor-suppressing. Ultimately, a more refined understanding of the contextual regulation of Wnt/β-catenin signaling will be essential for addressing if and how therapeutic targeting of this pathway could be leveraged for patient benefit.